Representing two of the major "first line of defense" systems of the human body, complement and coagulation engage in intense crosstalk. For example, several proteases of the coagulation stystem have been show to directly activate complement proteins such as C3 and C5. Likewise, certain complement enzymes (e.g., MASP-2) were described to act on proteins of both the complement and the coagulation system. Complement may also amplify coagulation and inhibit fibrinolysis through C5a, which induces the expression of tissue factor and plasminogen-activator inhibitor 1. Such crosstalk mechanisms are also likely involved in many thromboinflammatory diseases. This functional map visualizes major interactions at the crossroads of these two homeostatic defense systems.